Erythema multiforme: distinguishing hypersensitivity reactions, drug allergy, or herpes simplex infection

Cutaneous reactions present a diagnostic challenge, mainly when multiple factors, such as infections, medications, and environmental triggers, contribute to the clinical picture. Erythema multiforme (EM) is an acute, self-limiting mucocutaneous disorder that is most commonly triggered by herpes simplex virus (HSV) but can also be associated with drug-induced hypersensitivity reactions. Diagnosing EM becomes even more complex in patients taking photosensitizing medications, such as doxycycline, which can cause phototoxic or photoallergic reactions. Differentiating between drug-induced and infection-associated EM, as well as distinguishing it from more severe conditions like Stevens-Johnson syndrome (SJS), is crucial for appropriate management. This case report presents a case of a 57-year-old Caucasian female with a history of penicillin allergy who developed a phototoxic reaction to doxycycline following sun exposure. She was treated with silver sulfadiazine for her skin lesions but subsequently developed EM, with target-like lesions predominantly on the legs and a concurrent herpes simplex labialis infection. Laboratory findings were unremarkable, and there was no mucosal involvement. Given the suspected drug-induced nature of the reaction and the presence of HSV, a cautious approach was taken. Treatment with oral prednisone led to the resolution of symptoms without recurrence. Patch testing for doxycycline and silver sulfadiazine was omitted due to the risk of severe cutaneous adverse drug reactions (SCARs) and their non-essential status. Instead, penicillin testing was prioritized due to its clinical importance, and the patient successfully passed the oral amoxicillin challenge. This case highlights the diagnostic challenges of differentiating between drug-induced, infection-triggered, and photosensitivity-related cutaneous reactions. A careful evaluation of medication history, infection status, and clinical presentation is essential to guide the management of this condition.